Isovaleric acidemia, also called isovaleric aciduria, is an autosomal metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.
A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.
In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.
The urine of newborns can be screened for isovaleric acidemia using mass spectrometry, allowing for early diagnosis.
Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States. The condition is inherited in an autosomal recessive pattern, caused by mutations in both copies of the IVD gene.
The enzyme encoded by IVD, isovaleric acid-CoA dehydrogenase (EC 22.214.171.124), plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for the third step in processing leucine, an essential amino acid. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, isovaleric acid and related compounds build up to toxic levels, damaging the brain and nervous system.
^ ab Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B (2006). "Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry". J Inherit Metab Dis.29 (2-3): 383-389. PMID 16763906.
^ Tokatli A, Oskun T, Ozalp I (1998). "Isovaleric acidemia. Clinical presentation of 6 cases". Turk J Pediatr.40 (1): 111-119. PMID 9673537.